The Effects of Aqueous Extract of Eryngium Campestre on Ethylene Glycol-Induced Calcium Oxalate Kidney Stone in Rats.

PURPOSE: This study aimed to evaluate the anti-inflammatory effect of E. campestre using the aqueous extracts, obtained from the aerial parts, on Ethylene Glycol (EG)-induced calcium oxalate kidney stone in rats. MATERIALS AND METHODS: 64 male Wistar rats were randomly divided into 8 groups. Group I was considered as negative control and received normal saline for 30 days, group II as kidney stone control received EG for 30 days, groups III to VI as prophylactic treatment received EG plus 100, 200 or 400 mg/kg extracts for 30 days and groups VI to VIII received EG as therapy from day one and 100, 200 or 400 mg/kg extract from the 15th day. On the 30thday from the start of induction, rats were euthanized. Blood was collected and the kidneys were immediately excised. Slides from each one's kidneys were prepared and stained with Hematoxylin & Eosin method. Also levels of interleukin-1 beta (IL-1?) and interleukin-6 (IL-6) were determined in rat's serum by competitive ELISA kit. RESULTS: E. campestre reduced IL-1? and IL-6 levels, showing a significant reduction for both cytokines in all prophylactic groups, especially at the dose of 400 mg/kg (P-value < .001). Moreover, IL-1? (p = .011) reduced significantly in the therapy groups in 400 mg/kg dose. Crystal count reduction was seen in all prophylactic and therapy groups in comparison with group II. CONCLUSION: These results suggest that the E. campestre extract has potent suppressive effect on pro-inflammatory cytokine production in rat. Also, E. campestre decreases crystal deposition in the kidney of the hyperoxaluric rat.

Analysis of the influence of the T393C polymorphism of the GNAS gene on the clinical expression of primary hyperparathyroidism / Análisis de la influencia del polimorfismo T393C del gen GNASen la expresión clínica del hiperparatiroidismo primario

Background: The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose Gsα subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT).Methods: An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman(R) SNP Genotyping assay. Results: The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects. Conclusion: Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation (AU)

Introducción: El receptor de la hormona paratiroidea y de la proteína relacionada con la hormona paratiroidea (PTH/PTHrp) está situado en la membrana celular de sus tejidos diana: riñón y osteoblastos. Se trata de un receptor unido a proteina G cuya subunidad Gsα está codificada por el gen GNAS. Nuestro objetivo fue estudiar si el polimorfismo de un sólo nucleótido (SNP) T393C del gen GNAS se asociaba con litiasis renal, densidad mineral ósea (DMO) o marcadores de remodelado óseo en el hiperparatiroidismo primario (HPTP). Métodos: Analizamos parámetros clínicos, bioquímicos y densitométricos en 3 zonas y su relación con el SNP T393C del gen GNAS en 261 pacientes con HPTP y en 328 controles sanos. El genotipado se realizó utilizando el ensayo Custom Taqman(R). Resultados: Las frecuencias genotípicas del SNP T/C 393 del GNAS fueron similares en ambos grupos control y HPTP. No encontramos ninguna asociación entre los genotipos y la expresión clínica del HPTP (litiasis renal y fracturas óseas). Encontramos una tendencia no estadísticamente significativa hacia una menor DMO en columna lumbar, cuello femoral y cadera en los sujetos control y HPTP portadores del alelo C. Conclusiones: No encontramos susceptibilidad genética para el desarrollo de PHPT relacionada con el polimorfismo T393C del gen GNAS ni influencia en su expression clínica. Sí hallamos una tendencia hacia niveles menores de DMO en el hueso trabecular relacionada con el alelo C en pacientes con PHPT y en sujetos control sin ser suficiente para sugerir una expresión clínica más grave. Estos resultados pueden ser considerados como un punto de partida para futuros estudios con mayor tamaño muestral y con evaluación funcional complementaria (AU)

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement.

BACKGROUND: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. DESIGN: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. RESULTS: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. CONCLUSIONS: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.

Nephrotoxicity of Natural Products.

BACKGROUND: The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. SUMMARY: This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. KEY MESSAGES: The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education.

Efecto antiurolitiásico de una formulación de las plantas Herniaria glabra, Agropyron repens, Equisetum arvense y Sambucus nigra (Herbensurina®) en un modelo experimental de nefrolitiasis en ratas / Antiurolithiasic effect of a plant mixture of Herniaria glabra, Agropyron repens, Equisetum arvense and Sambucus nigra (Herbensurina®) in the prevention of experimentally induced nephrolithiasis in rats

OBJETIVO: Determinar el efecto preventivo sobre la litiasis renal de una formulación botánica formada por Herniaria glabra, Agropyron repens, Equisetum arvense y Sambucus nigra en un modelo experimental de nefrolitiasis en ratas. MÉTODOS: Seis grupos de animales con seis ratas Wistar macho cada uno fueron inducidos a nefrolitiasis mediante el tratamiento con etilenglicol (EG) 0,75% y cloruro de amonio 1% durante tres días y posteriormente con EG durante 15 días más. Un grupo fue tratado con placebo (grupo control) y los otros grupos (grupos tratados) fueron tratados con 30 mg/Kg, 60 mg/Kg, 125 mg/Kg, 250 mg/kg y 500 mg/Kg de la formulación de extractos de plantas (FEP). Se midió el volumen de agua ingerida y de orina excretada durante 24 h en diferentes días del experimento y se determinó la diuresis, cristaluria y bioquímica. Se realizó el análisis histológico del riñón. La caracterización fitoquímica de la FEP se realizó mediante técnicas cromatográficas. RESULTADO: La cantidad de depósitos de cristales de oxalato de calcio (OxCa) de los animales tratados con 125 mg/Kg de la FEP y el número de microcalcificaciones en todos los grupos tratados con la FEP fue menor comparado con el grupo control, siendo las diferencias estadísticamente significativas (d. e. s.). La presencia de fibrosis subcapsular fue mayor en el grupo control que en los grupos tratados (d. e. s.). La diuresis de los grupos tratados con 125 mg/Kg y 500 mg/Kg de la FEP fue mayor que la del grupo control (d. e. s.). El análisis fitoquímico demostró la presencia de flavonoides, ácidos dicarboxílicos y saponinas. CONCLUSIONES: La administración de la FEP previene la formación de cristales de OxCa y de microcalcificaciones en el riñón y disminuye el riesgo de fibrosis subcapsular renal. La dosis de 125 mg/Kg de la FEP es la que presenta un mayor efecto sobre los parámetros estudiados

OBJECTIVE: To determine the effect of a botanical formulation of Herniaria glabra, Agropyron repens, Equisetum arvense, and Sambucus nigra as a preventive agent in an experimentally induced nefrolithiasis model in rats. METHODS: Six groups of six Wistar male rats each were induced for nefrolithiasis by treatment with 0.75% ethylene glycol (EG) and 1% ammonium chloride for three days and then EG only for 15 days. One group was treated with placebo (control group) and the other groups (treated groups) were treated with 30 mg/Kg, 60 mg/Kg, 125 mg/Kg, 250 mg/Kg and 500 mg/Kg of the plant extract formulation (PEF). 24-h urine and water samples were collected one day before EG administration and at 7, 13 and 18 days to determine diuresis, crystalluria and urine biochemistry. The kidneys were removed for histological analysis. The phytochemical characterization of PEF and each of its component plant extracts was performed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. RESULTS: Animals treated with 125 mg/Kg of the PEF had statistically significantly lower calcium oxalate crystals deposits content compared to the control group. All PEF doses statistically significantly decreased the number of microcalcifications compared to the control group. Furthermore, the number of kidneys affected by subcapsular fibrosis was statistically significantly higher in control group than in treated groups with the PEF. The diuresis of the 125 mg/Kg and 500 mg/Kg PEF-treated groups was statistically significantly higher than that of the control group. A phytochemical analysis demonstrated the presence of flavonoids, dicarboxylic acids and saponins. CONCLUSIONS: Treatment with PEF prevents deposits of calcium oxalate crystals formation and of microcalcifications in the kidney, and reduces the risk of fibrosis subcapsular. 125 mg/Kg of PEF is the dose that has a greater effect on the studied parameters

Biochemical determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis.

OBJECTIVE: To analyze the biochemical alterations in plasma and the urine determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis. METHODS: We performed a cross-sectional study of 120 patients divided into 2 groups: group 1, 60 patients without nephrolithiasis; and group 2, 60 patients with severe and/or recurrent calcium nephrolithiasis. In all patients, a study of renal function, calcium metabolism, and bone remodeling markers, and a study of the lithogenic factors were performed in urine after fasting and in 24-hour urine samples. RESULTS: We observed greater values for phosphorus in group 1 than in group 2 (P=.03). Also, we found greater values for intact parathyroid hormone (P=.01), osteocalcin (P=.000), and ß-crosslaps (P=.000) in group 2 than in group 1. In the 24-hour urine samples, significant differences were found between groups 1 and 2 in calciuria (11.7 vs 17.4 mg/dL; P=.000), citraturia (50.6 vs 33.5 mg/dL; P=.002), calcium/creatinine quotient (0.14 vs 0.20; P=.001), calcium/citrate quotient (0.05 vs 0.13; P=.04), and calcium/creatinine quotient after fasting (0.09 vs 0.16; P=.000). CONCLUSION: We consider the determinants of severe and/or recurrent calcium lithiasis to be hypercalciuria and hypocitraturia and a calcium/citrate quotient>0.06. As risk markers we can consider phosphatemia<2.9 mg/dL, phosphate/chlorine quotient>35, alkaline phosphatase>80 U/L, intact parathyroid hormone>60 pg/mL, osteocalcin>16 ng/mL, ß-crosslaps>0.400 ng/mL, and ß-crosslaps/osteocalcin quotient>0.028.

Indicación actual de la cirugía abierta en el tratamiento de la litiasis renal. Ureterocalicostomía como tratamiento definitivo de litiasis en mujer con patología renal / Current indications of open surgery for the treatment of renal lithiasis. Ureterocalycostomy as definitive treatment for lithiasis in a female with recurrent dis

OBJETIVO: Presentamos un caso de litiasis recidivante asociado a alteración anatómica de la pelvis renal secundaria a cirugía.MÉTODOS/RESULTADOS: La paciente presenta un episodio de infección urinaria complicada con pionefrosis y septicemia. En la urografía intravenosa se observa litiasis radiodensa infecciosa, pielolocalicial múltiple compleja, sobre riñón con hidronefrosis grado III-IV por importante esclerosis piélica secundaria a cirugía previa sobre dicha unidad renal. Se realiza nefrectomía polar inferior con nefrolitotomía y reconstrucción de la vía urinaria superior mediante uréterocalicostomía. Dos años y medio después de la cirugía la urografía de control refleja ausencia de litiasis y leve retraso de la función renal.CONCLUSIONES: La ureterocalicostomía está indicada en casos de obstrucción de la unión ureteropiélica asociada a una pelvis intrarrenal por alteraciones de la fusión, rotación o localización renal, y en casos de fibrosis peripiélica severa secundaria a una pieloplastía fallida o cirugía renal previa. En el caso presentado además del componente infeccioso de las litiasis, una alteración anatómica, probablemente secundaria a la cirugía previa, provocaba una perpetuación de la clínica litiásica. Ante tal sospecha se impuso una solución de tipo quirúrgico que solucionara en un tiempo tanto la eliminación de la litiasis como una correcta derivación de la zona funcionante del riñón para evitar recidivas posteriores(AU)

OBJECTIVE: We describe one case of recurrent lithiasis associated with anatomical alteration of the renal pelvis related to previous surgery.METHODS/RESULTS: The patient presented a urinary tract infection episode, complicated with pyonephrosis and septi-cemia. In the intravenous urography, infectious radiopaque pyelocaliceal multiple and complex lithiasis can be seen, as well as kidney hydronephrosis grade III-IV. Important pyelic sclerosis secondary to previous surgery on the renal unit was seen. Nephrectomy was performed with lower pole nephro-lithotomy and reconstruction of the upper urinary tract through ureterocalicostomy. Two and a half years after surgery, control urogram shows absence of urolithiasis and a slight delay of renal function.CONCLUSIONS: Ureterocalicostomy is indicated in cases of ureteropelvic junction obstruction associated with intrare-nal pelvis caused by alterations of fusion, rotation or location of kidney. It is also indicated in cases of severe peripyelic fibrosis secondary to previous pyeloplasty failure or renal sur-gery. In our case, in addition to the infectious component of lithiasis, an anatomical alteration, probably secondary to previous surgery, caused the chronification of lithiasis. Fa-cing such suspicion a surgical management was undertaken to eliminate the lithiasis and get a correct derivation of the working area of the kidney, in order to prevent further recu-rrences(AU)

Silicate nephrolithiasis after ingestion of supplements containing silica dioxide.

Silicate calculi are common in some mammals, such as dogs and sheep, but extremely rare in humans. We report a case of silicate calculi in a woman using oral over-the-counter Uncaria tomentosa, Digestive Advantage and FlexProtex supplements. All 3 contained the excipient silica dioxide. Stone analysis showed composition of 100% silicate. The nephrolithiasis promptly abated after discontinuation of the products containing silica, then returned when the patient restarted her supplements. This case emphasizes the importance of stone analysis when obvious causes of nephrolithiasis are unclear and highlights the concerns of using over-the-counter supplements without substantial oversight.